NIH Awards Crinetics $2.4 Million to Develop Congenital Hyperinsulinemia, Cushing’s Therapies

Crinetics Pharmaceuticals has received two grants from the National Institutes of Health’s (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to develop nonpeptide, oral somatostatin agonists for congenital hyperinsulinemia and new therapies for Cushing’s disease.

The two Small Business Innovation Research (SBIR) grants, totaling $2.4 million, include a fast-track grant of up to $2.1 million to develop the nonpeptide agonists, and a Phase 1 discovery grant of $300,000 to seek new small molecule therapies for Cushing’s disease.

Congenital hyperinsulinism (CHI) is the most severe form of hyperinsulinemic hypoglycemia (HH), a condition characterized by persistent low blood sugar due to excessive insulin production. CHI can cause seizures, developmental delays, and learning disabilities. CHI results from genetic mutations in the insulin secretion pathway.

No treatments currently exist that specifically target chronic hypoglycemia precipitated by CHI, and current therapeutic options are limited to repurposed drugs. Although they might not have optimal outcomes, these drugs are prescribed because the next line of treatment is partial or full pancreatectomy, an invasive and serious procedure that does not guarantee results and often leaves patients diabetic.

Cushing’s syndrome causes the growth of fat pads in different parts of the body, excessive sweating, dilation of capillaries, thinning of the skin, muscle weakness, hyperglycemia, and heart disease, among other metabolic disturbances. If not adequately controlled, it can be life-threatening.

Cushing’s disease is the most common manifestation of Cushing’s syndrome, caused by benign, slow-growing tumors in the pituitary gland that secrete excess adrenocorticotropic hormone (ACTH), which increases cortisol levels.

The surgical removal either of the ACTH-secreting tumor in the pituitary gland or the adrenal glands themselves is the first line treatment for Cushing’s disease. The procedure is not risk-free, however, and often is unsuccessful. Alternative treatment options include inhibitors of steroid synthesis enzymes that prevent the production of cortisol and improve symptoms, but as with any other steroids, unwanted side effects are common.

Crinetics is a company specialized in developing therapeutic solutions for endocrine disorders and endocrine-related cancers.

“We are delighted with the NIH’s continuing support of our programs to develop new drugs for patients with rare endocrine disorders,” Stephen Betz, PhD, founder and vice president of biology at Crinetics, said in a press release. “These awards will enable us to advance our efforts in both hyperinsulinemia and Cushing’s disease, expanding our pipeline to include these diseases with significant unmet medical needs, and bring these treatments to the patients who need them.”